Sedative-hypnotics

Propofol Midazolam Etomidate Thiopentone Ketamine

•Phenol derivative •Benzodiazepine •Imidazole derivative •Barbiturate •Phencylidine

•GABA receptor •GABA receptor •GABA receptor •GABA receptor •Inhibit NMDA
agonist causing ↑ Cl agonist causing ↑ Cl agonist causing ↑ Cl agonist causing ↑ Cl receptor
influx influx influx influx

•1-2mg/kg •0.1-0.2 mg/kg •0.15-0.3 mg/kg •3-5 mg/kg •2-4 mg/kg

•2-4 mg/kg/hr •0.02-0.1 mg/kg/hr •No infusion dose •3-5 mg/kg/hr •5-25 ug/kg/min

• Onset – 1-2 min

• Duration – 6-10 min
Propofol Midazolam Etomidate Thiopentone Ketamine

•Hypotension, •Hypotension, •Cardiac stable •Hypotension, •HTN, tachycardia

bradycardia tachycardia (minimal ↓ bp and tachycardia •Maintain airway,
•Apnoea •Apnoea CO) •Apnoea bronchodilation
•↓ ICP, cerebral •Muscle relaxant, •Apnoea •↓ ICP, cerebral •Dissociative
MRO2 and IOP sedative, hypnotic, •↓ ICP, cerebral MRO2 and IOP anaesthesia
•Anti-emetic anxiolytic, antegrade MRO2 and IOP •↑ CBF, ICP, IOP
•Propofol infusion amnesia, anti- •Vomiting •↑ salivation
syndrome epileptic •Inhibit
steroidogenesis

•A – inactive orally •A – 44% oral •A –inactive orally •A – 100% oral •A – 20% oral
•D – 98% protein bioavailability •D – 76% protein bioavailability bioavailability
bound •D – 96% protein bound. Short •D – 60% protein •D – 50% protein
•M – liver bound duration of action bound. 40% in RBCs. bound. Short
•E – urine. t1/2 = 10- •M – liver due to redistribution Rapid onset due to duration due to
60 minutes •E – urine. t1/2 = 2-4 •M – plasma and lipophilic and less redistribution
hours hepatic esterase ionized •M – liver
•E – urine and bile. •M – liver •E – urine and bile.
t1/2 = 2-4 hours •E – urine and bile. t1/2 = 2-3 hours
t1/2 = 3-22 hours
Others
Analgesia Opioids

• Local anaesthetic • Strong agonists

• GABA agonist -morphine, heroine
• 5-HT antagonist -fentanyl, pethidine
• NMDA antagonist -methadone

• Moderate agonists
-codeine
-loperamide
-tramadol***

• Mixed agonist+antagonists
NSAIDs -nalbuphine
-buprenorphine
• Non-specific COX inhibitors
-aspirin • Antagonists
-diclofenac -naloxone
-mefenamic acid -naltrexone
-ibuprofen

• COX-2 selective inhibitors

-celecoxib
-meloxicam
NSAIDs
 Opioids
Morphine Fentanyl Pethidine Heroine Tramadol

•Natural •Synthetic •Semi-synthetic •Natural •Synthetic

•u, k and δ opioid •u (main), k and δ •u, k and δ opioid •u, k and δ opioid •Weak u, k and δ
receptor agonist at opioid receptor receptor agonist at receptor agonist at opioid receptor
spinal and agonist at spinal and spinal and spinal and agonist.
supraspinal level supraspinal level supraspinal level supraspinal level •α receptor
•Stimulates histamine •Minimal histamine •Less histamine •Stimulates histamine antagonist
release*** release release*** release*** •5-HT agonist

•0.05-0.1 mg/kg •0.5-1 ug/kg •0.5-1 mg/kg •Drug of abuse •1-2 mg/kg

•Onset – 30-60 •Onset – 5-15 •Onset – 5-15 •Onset – •Onset – 30-60

minutes minutes minutes •Duration – minutes
•Duration – 3-4 hours •Duration – 4-6 hours •Duration – 2-3 hours •Duration – 2-4 hours
Morphine Fentanyl Pethidine Heroine Tramadol

•Hypotension***, •Bradycardia. •Hypotension***, •Hypotension***, •CVS stable

bradycardia Minimal hypotension. tachycardia bradycardia •RS stable
•RS depression, Obtunds CVS •RS depression •RS depression, •Analgesia
bronchospasm*** response during •Analgesia, sedation, bronchospasm*** •Vomiting. Minimal
•Analgesia, sedation, intubation miosis, seizure •Analgesia, sedation, constipation, colic
miosis, seizure •RS depression, chest •Constipation, miosis, seizure
•Constipation, wall rigidity vomiting, urinary •Constipation,
vomiting, urinary •Analgesia (x60 retention, colic vomiting, urinary
retention, colic potency), miosis. •↑ ADH secretion retention, colic
•Pruritis*** Minimal sedation •Pruritis***
•↑ ADH secretion •Constipation, urinary •↑ ADH secretion
retention, colic

•A – 50% oral •A – 33% oral •A –75% oral •A – •A – 80% oral

biovailability bioavailability bioavailability •D – bioavailability
•D – 40% protein •D – 90% protein •D – 67% protein •M – •D – 20% protein
bound bound. Short bound •E – bound
•M – glucuronidation duration due to rapid •M – demethylation •M – demethylation
in liver redistribiution and hydrolysis in liver in liver
•E – urine. t1/2 = 2-4 •M – dealkylation and •E – urine. t1/2 = 2-6 •E – urine and bile.
hours hydroxylation in liver hours t1/2 = 4-6 hours
•E – urine. t1/2 = 2-14
hours
 Drugs acting on GABA-ergic
neurons
GABA transaminase inhibitor
-inhibit GABA metabolism by
GABA transaminase

-vigabatrine GABA reuptake inhibitor

-inhibit GABA reuptake by
presynaptic neuron

-tiagabine

GABA mimetics
-direct stimulation of GABA
receptors

-barbiturates
-benzodiazepines
-propofol
 Drugs acting on NMDA-ergic
neurons

Glutamate release inhibitor NMDA receptor antagonist

-inhibits glutamate release -direct inhibition of NMDA
receptor
-topiramate
-ketamine
 Drugs acting at other/multiple sites

Na channel blocker Ca channel blocker

-inhibits pre and post -inhibits pre and post
synaptic neuron Na channel synaptic neuron Ca channel

-phenytoin -ethosuximide
-carbamazepine
-lamotrigine

Others
-valproate -acts on both GABA and NMDA receptors and Na channel

-levetiracetam - unknown
 Class I (Na channel blocker) Class III (K channel blocker)
• Ia – quinidine, procainamide -amiodarone
• Ib – lignocaine, mexiletine -sotalol
• Ic – flecainide, propafenone

Anti-arrhythmia Class IV (Ca channel blocker)

-verapamil
Class II (B blocker) -diltiazem
-propranolol
-esmolol

Class V (Others)
-adenosine
-Mg
-K
-digoxin
-atropine
Centrally acting
-α2 agonists

α2 agonists
-methyldopa Heart
-clonidine -B blockers

Anti-HTN
B blockers

• Non specific
- +ISA -oxyprenolol
- -ISA -propranolol, timolol,
sotalol

• B1 specific
- +ISA -celeprolol
- -ISA -metoprolol, esmolol,
bisoprolol, atenolol

• + α1 blocking property
-labetolol
 • α1 antagonists
Kidney -prazosin, terazosin, phentolamine,
-diuretics phenoxybenzamine

• ACE inhibitors
-captopril, perindopril, enalapril
Diuretics
• AT-II blockers
• Loop diuretics -losartan, valsartan, candersatan
-frusemide, bumetanide
• CCB
• Thiazides -dihydropyridine - amlodipine,
-HCTZ nifedipine
-nondihydropyridine - verapamil,
• K-sparing diuretic diltiazem
-spironolactone
• Vasodilators
• CA inhibitor -GTN, hydralazine, nitroprusside
-acetazolamide

• Osmotic diuretic
-mannitol
Blood vessels
-α1 antagonists
-ACE inhibitors
-AT-II blockers
-CCB
-vasodilator
Anti-platelet
Anti-coagulant
Streptokinase
-not a protease (no enzymatic activity)
-binds to plasminogen (free and clot-bound) to form a
complex and releases plasmin
-↑ fibrinolysis and fibrinogenolysis Thrombolytics

tPA (tissue plasminogen activator)

-a protease (has enzymatic activity)
-binds to plasminogen (selectively to clot-bound) and lyses
it to plasmin
-↑fibrinolysis and ↓ fibrinogenolysis
Sympathomimetics Phosphodiesterase III Calcium sensitizing Others
inhibitors agents
-vasopressin
Natural -milrinone -levosimenden -digoxin
catecholamines -amrinone -Ca2+
-glucagon
-adrenaline
-noradrenaline
-dopamine

Synthetic

Vasopressors and inotropes

cathecolamines

-dobutamine
-isoprenaline
-dopexamine

Non catecholamines

-ephidrine
-phenylephrine
B2 agonists Muscarinic antagonists

• Short acting -ipratropium Br

-salbutamol -tiotropium Br
-terbutaline

• Long acting
-salmeterol
-formeterol
Methylxanthines
• Catecholamines
-adrenaline -theophylline

Mast cell stabilizer

-Na chromoglycate

Corticosteroids
Lipoxygenase inhibitors
• Systemic
-zileuton -hydrocortisone
-prednisolone

Leukotrine receptor • Inhaled

antagonists -budesonide
-beclamethasone
-zafirlucast -fluticasone
-montelucast
Carbonic anhydrase inhibitors Thiazide diuretics K sparing diuretics

-acetazolamide -hydrochlorothiazide -spironolactone

-dorzolamide -chlorothiazide -eplerenone
-methazolamide -bendroflumethiazide -amiloride
-triamterene

Diuretics
Osmotic diuretics

-mannitol
-isosorbide
-urea
-glycerine

ADH receptor antagonist

Loop diuretics Thiazide-like diuretics
-conivaptan
-furosemide -chlorthalidone -tolvaptan
-bumetanide -indapamide
-ethacrynic acid -metolazone
Insulin Dipeptidyl peptidase-4 inhibitor
-sitagliptin
• Ultra short acting
-lispro, aspart
Thiazolidinediones
• Short acting -pioglitazone, rosiglitazone
-humulin R, novolin R

• Intermediate acting
-humulin N, novolin N
Anti-DM
• Long acting Insulin secretagogues
-glargine, determir
• Sulphonylureas
-1st gen - tolbutamide
-2nd gen - gliclazide, glibenclamide

• Meglitinides
Biguanides
-repaglinide
-metformin
• D-phenylalanine derivative
-nateglinide
α glucosidase inhibitors
-acarbose, miglitol
Corticosteroids
Cell wall synthesis inhibitors Cephalosporins
-penicillin
-cephalosporins • 1st generation
-B-lactamase inhibitors -cefazolin, cephalexin

-monobactam • 2nd generation

-carbapenem -cefuroxime, cefaclor
-glycopeptide
-teicoplanin, bacitracin • 3rd generation
-ceftriaxone, ceftazidime

• 4th generation
-cefepime
Penicillin

• Penicillin Others
-penicillin V, pencillin G,
benzathine penicillin • Carbapenem
-imipenem, meropenem
• Anti-staphylococcal
-cloxacillin, methicillin, nafcillin • Monobactam
-aztreonam
• Extended spectrum
-amoxicillin, ampicillin, • Glycopeptide
piperacillin, -vancomycin

B lactamase inhibitors
-clavulanic acid, tazobactam,
sulbactam
Free radical generator Nucleic acid synthesis inhibitors
-metronidazole -folate antagonist
-nitrofurantoin - DNA gyrase inhibitor
- RNA polymerase inhibitor
- Free radical generator

RNA polymerase inhibitors

-rifampicin
Folate antagonists

• Sulfonamides
-sulfamethoxazole, sulfadiazine,
sulfasalazine
DNA gyrase inhibitors
• Pyrimidines
• Fluroquinolones -trimethoprim
-ciprofloxacin, levofloxacin,
ofloxacin
 50s inhibitors

• Macrolides
-azithromycin, clarithromycine,
erythromycin

Chloramphenicol

Clindamycin

Oxazolidinones
-linezolid

Protein synthesis inhibitors

• 50s inhibitor
30s inhibitor -macrolides
-chloramphenicol
• Aminoglycosides -clindamycin
-gentamycin, neomycin, -oxazolidinones
streptomycin
• 30s inhibitor
• Tetracycline -aminoglycosides
-doxycycline, demeclocycline -tetracycline
 Synthesis
Lipoxygenase inhibitors
-zileuton
Phospholipase C inhibitors
-costicosteroids

5-lipoxygenase activating protein

COX 1 and 2 inhibitors
-NSAIDs

Leukotrine receptor
antagonists
-zafirlukast
-montelukast

Prostaglandins and leukotrines

Functions

• Anti-inflammatory PG
- PGE2, PGI2

• Pro-inflammatory PG
- PGD2, PGF2, TXA2
-all leukotrines
Leukotrines Vasoconstriction
Bronchospasm ↑ mucus
secretion and oedema
Eosinophilia and chemotaxis